The major objective of this study is to develop a comprehensive understanding of the keratinization process in order to more fully understand the numerous disorders which involve epidermis, hair and nail. Since the fibrous proteins play a major role emphasis will be placed on them, but other important structural components, keratohyalin and cornified cell envelope, will also be investigated. These studies will be done in whole tissue as well as in cultured epidermal cells with the aim of using epidermal cell culture to study the metabolic disturbances in a number of disorders of keratinization including psoriasis and several types of ichthyosis. Epidermal cell culture will be used to study mechanism of disease and the effect of various hormones and chemicals on normal epidermal cells as well as diseased cells. This will include basal cell carcinoma. The epidermal enzyme which converts peptide bound argininge to peptide bound citruline will be purified and characterized and the natural substrates will be identified. The precursors of the cornified envelope of human keratinocytes will be identified in cultured cells and whole tissue by use of labelled probes as well as immunologic techniques. The procursors of keratohyalin granules in cultured rat epidermis will be identified by labelled histidine incorporation and immunologic techniques. The factors influencing the composition of fibrous proteins will be investigated. We shall ccntinue our studies of inherited disorders of keratinization so that patient material will be available for laboratory study.